title: Nicotinamide adenine dinucleotide (NAD+) repletion attenuates bupivacaine-induced neurotoxicity.
abstract: Bupivacaine is one of the most toxic local anesthetics but the mechanisms underlying its neurotoxicity are still unclear. Intracellular nicotinamide adenine dinucleotide (NAD(+)) depletion has been demonstrated to play an essential role in neuronal injury. In the present study, we investigated whether intracellular NAD(+) depletion contributes to bupivacaine-induced neuronal injury and whether NAD(+) repletion attenuates the injury in SH-SY5Y cells. First, we evaluated the intracellular NAD(+) content after bupivacaine exposure. We also examined the cellular NAD(+) level after pretreatment with exogenous NAD(+). We next determined cell viability and the apoptosis rate after bupivacaine treatment in the presence or absence of NAD(+) incubation. Finally, cell injuries such as nuclear injury, reactive oxygen species (ROS) production, and mitochondrial depolarization were detected after bupivacaine treatment with or without NAD(+) pretreatment. Bupivacaine caused intracellular NAD(+) depletion in a time- and concentration-dependent manner. Cellular NAD(+) replenishment prevented cell death and apoptosis induced by bupivacaine. Importantly, exogenous NAD(+) attenuated bupivacaine-induced nuclear injury, ROS production, and mitochondrial depolarization. Our results suggest that NAD(+) depletion is necessary for bupivacaine-induced neuronal necrosis and apoptosis, and that NAD(+) repletion attenuates neurotoxicity resulting from bupivacaine-treatment.
authors.affiliation: Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, 253 Industrial Road, Guangzhou, 510280, Guangdong Province, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zheng
authors.forename: Shi Yuan
authors.initials: SY
authors.lastname: Xu
authors.forename: Shu Qin
authors.initials: SQ
authors.lastname: Zhou
authors.forename: Lu Ying
authors.initials: LY
authors.lastname: Lai
authors.forename: Le
authors.initials: L
authors.lastname: Li
mesh_terms: D002045:Bupivacaine / Q000494:pharmacology; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D006801:Humans; D008012:Lidocaine / Q000494:pharmacology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009243:NAD / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D009243:NAD; D008012:Lidocaine; D002045:Bupivacaine